The present invention relates both to a membrane composed of cellulose which has an improved surface, and to a process and an apparatus serving the manufacture of such membrane, the latter having application in particular to rapid diagnostic tests that are used to identify specific analytes present in fluid media.
Membranes composed of cellulose are frequently employed in the manufacture of dry reagents, and, more particularly, of test strips that are used in analysis and in medical diagnostics (diagnostic membranes). U.S. Pat. No. 5,628,960 discloses both such a symmetrical membrane comprising a polymer blend of cellulose nitrate and cellulose acetate which, containing micropores, is supported on a polyester carrier film, and a method for the production thereof. In the prior art rapid diagnostic tests employed to identify specific analytes, for example in human, animal and vegetable organisms, in food and in the environment, the requirement to bind proteins or protein-like substances used as analytes and the requirement to have large pore sizes, necessitates the use of membranes containing primarily cellulose nitrate as the dry reaction phase, since only this type of membrane can satisfy both of the aforementioned requirements. Such membranes are chiefly produced from critical casting solutions in a so-called evaporation process in which the underlying formation mechanism is based on a phase inversion.
This process permits the manufacture of microfiltration membranes comprising primarily cellulose nitrate and having pore widths ranging between approx. 0.01 and at least 12 μm. One disadvantage attending this process is that, beyond a pore width of approx. 0.45 μm, and, more particularly with respect to the membranes which being normally used in diagnostic applications, exhibit pore widths>0.45 μm, a distinct tendency to form so-called filter dust has been observed, resulting from the unwanted fractionated precipitation of the polymers during the phase inversion process.
The filter dust fraction is formed from the non-membrane-forming, low molecular portion of the commercially available feedstocks used which precipitate out chiefly in the form of a more or less loosely packed layer of dust or irregularly formed deposits on the surface of the membrane and, more noticeably, on the upper side of the heretofore prepared integrated membrane layer.
Most of the cellulose nitrate membranes that are employed for diagnostic purposes are in a film-supported format. Currently, such membranes are, for economic reasons, no longer produced by laminating the cellulose nitrate membrane onto an adhesive-coated film, but are rather produced by pouring membrane casting solutions directly onto a film as disclosed in Beer et al., U.S. Pat. No. 5,628,960.
It will, of course, be appreciated that the appearance of filter dust in such an arrangement is particularly problematic, since during the manufacture of such membranes, the casting solution can be applied only to the critical upper side of the membrane upon which filter dust has accumulated. Such deposits for a variety of reasons pose a major problem with respect to application in quick diagnostic tests. Due to differences in structure existing between the membrane layer and the filter dust deposit, the test liquids that are poured onto the membrane will migrate at different velocities on top or bottom, the result whereof being the formation of two separate traveling fronts over a broad, diffuse zone. The filter dust deposit moreover distorts the shape of the test lines and weakens the intensity of the resulting colour signals. These problems raise doubt as to the crucial precision and information value of the tests with respect to image sharpness, sensitivity, reproducibility and clarity.
A prior art process for eliminating the aforementioned problem consists of reprecipitating commercially available feedstocks in order to remove the low molecular components prior to using such feedstocks in the manufacture of the membrane. See Perl, German Patent No. DE 37 08 946 C1 and Beer et al., U.S. Pat. No. 5,628,960 (=DE 44 38 381). The disadvantages attending this multi-phase process are its complexity, its cost and its inefficiency.